1. Microbial Challenge Host Immuno- inflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Environmental and acquired risk factors Genetic risk factors Page, Ann Periodontol 1998 Pathogenesis of Periodontitis

2. Microbial Challenge Host Immuno- inflammatory response Clinical signs of disease initiation and progression Page, Ann Periodontol 1998 Bacteria attacking the body Antigens Lipopolysaccharides Other virulence factors

3. Pathogenesis of Periodontitis Microbial Challenge Host Immuno- inflammatory response Clinical signs of disease initiation and progression Page, Ann Periodontol 1998 Bacteria attacking the body Antigens Lipopolysaccharides Other virulence factors The body defense: Antibodies Neutrophils

4. Microbial Challenge Host Immuno- inflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Page, Ann Periodontol 1998 Inflammatory response releases: Cytokines Prostanoids Matrix Metalloproteinases Pathogenesis of Periodontitis

5. In Patient A, who is NOT susceptible to periodontitis: Microbial Challenge Host Immuno- inflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Page, Ann Periodontol 1998 Tissue and bone repair/healing

6. In Patient B, who is susceptible to periodontitis: Microbial Challenge Host Immuno- inflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Page, Ann Periodontol 1998 Tissue destruction and bone loss

7. Microbial Challenge Host Immuno- inflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Page, Ann Periodontol 1998 Deepening of periodontal pockets, furcation involvement, contaminated cementum… In Patient B, who is susceptible to periodontitis:

8. Microbial Challenge Host Immuno- inflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Environmental and acquired risk factors Genetic risk factors Page, Ann Periodontol 1998 Pathogenesis of Periodontitis

9. In periodontitis, what is actually occurring in a periodontal pocket…

10. Periodontal Pathogens has invaded: Periodontal pocket Cementum Gingival tissue In a patient susceptible to periodontitis, how does the body react?

11. 1. Epithelial Cells produce IL-8 and ICAM-1 in response to bacteria & antigens IL-8/ICAM-1

12. 2. IL-8 and ICAM-1 are chemotactic signals for neutrophils, which are recruited to the sulcus Neutrophils Bacteria/Antigens

13. 3. Neutrophils control bacterial assault by phagocytosis but also secrete matrix metalloproteinases or collagenases (MMP-8) which results in collagen degradation MMP-8

14. 4. Interaction of antigens with B cells lead to production of antibodies and complements, which contribute to phagocytosis B-cell Plasma Cell T-cell

15. 5. In response to bacterial LPS, various cells produce IL-1 , TNF- , and PGE2 Activated B-Cell LPS Macrophage Fibroblast IL-1  TNF-  PGE2

16. Activated B-Cell Macrophage Fibroblast IL-1  TNF-  Osteoclast activation PGE2 6. Production of IL-1 , TNF- , and PGE2 leads to osteoclast activation, proliferation and differentiation

17. Higher amounts of IL-1 , TNF- , PGE2, MMPs DiseaseHealth Lower amounts of IL-10, TGF- , IL- 1ra, TIMPs Major Mediators Proinflammatory Destructive

18. Lower amounts of IL-1 , TNF- , PGE2, MMPs DiseaseHealth Higher amounts of IL-10, TGF- , IL- 1ra, TIMPs Anti-inflammatory Protective